The innate lymphoid cell immune response in the mouse female genital tract upon infection with Chlamydia muridarum

Abstract: The immune cell group of innate lymphoid cells (ILCs) is represented by well-studied natural killer (NK) cells and Lymphoid tissue inducer (LTi) cells, as well as by recently discovered helper-like populations. It is known that these cells, which belong to the innate immune system, contribute to tissue homeostasis and repair as well as to the defence against some pathogens. As ILCs are mainly located at mucosal barrier surfaces, this study focusses on the investigation of ILCs in the female genital tract (FGT), an organ that is barely studied in this regard. A well-established mouse genital tract infection model is the infection with Chlamydia muridarum, a pathogen that can lead to severe long-term sequelae and tissue damage. This model was used to investigate the reaction of ILCs in the mouse FGT upon infection.
The results of this work show that all analysed ILC subsets respond to chlamydial infection, as detectable by changes in absolute cell numbers in the FGT. While trNK cells are the dominating ILC population in the FGT of uninfected mice, they are outnumbered by cNK cells that infiltrate the tissue upon chlamydial infection. The main site of ILC accumulation is the oviduct for all analysed subsets except for trNK that mainly expand in number in the uterine horns. During infection, ILC3 cells convert into an ILC1 phenotype, which may aid to support the clearance of Chlamydia. ILC2 numbers decrease during the early course of infection in a process that is not controlled by mitochondrial apoptosis.
To examine the influence of neutrophils and inflammatory monocytes on the accumulation of ILCs, Mcl-1-/- (lacking neutrophils) and Ccr2-/- (defective in monocyte recruitment) mice were infected with C. muridarum. It was shown that all analysed ILC subsets are influenced by the lack of these myeloid populations, however lack of neutrophils seems to affect the ILC immune response even more strongly than the loss of inflammatory monocytes.
Although no chlamydial genome copies were detectable in the FGT 30 days post infection, and although no TNF and IFNγ was produced by ILCs at this time point, the absolute number of NK cells and ILC1 cells was higher than in uninfected mice. This suggests that there must be stimuli present in the FGT that promote the accumulation of these ILCs when no Chlamydia are detectable any longer. Also, absolute ILC numbers are higher in oviducts with hydrosalpinx-formation compared to oviducts that do not show macroscopical tissue damage at later time points of infection. The absolute number of all ILC subsets as well as of neutrophils, monocytes and T cells correlated with the degree of oviduct damage. Concerning the correlation between ILCs in the uterine horns and the corresponding tissue weight, a significant correlation was only observed for cNK and ILC1 cell numbers while trNK cell number and ILC2s did not show this effect. Taken together, these results suggest a possible contribution of ILCs in the process of tissue damage

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2020

Klassifikation und Themen

• Schlagwort: Infection ; Mice ; Chlamydia ; Immune response ; Generative organs, Female ; Chlamydia

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: Barth, Svenja
• Beteiligte Personen und Organisationen: Häcker, Georg ; Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie

Weitere Informationen

• DOI: 10.6094/UNIFR/176189
• URN: urn:nbn:de:bsz:25-freidok-1761894
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:50 MEZ